SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

Autor(es)

Silveira, Vanessa Silva ; Borges, Kleiton Silva ; Santos, Verena Silva ; Ruckert, Mariana Tannus ; Vieira, Gabriela Maciel ; Vasconcelos, Elton Jose Rosas ; Nagano, Luis Fernando Peinado ; Tone, Luiz Gonzaga ; Scrideli, Carlos Alberto

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1, p. 7-pg., 2020-09-16.

Resumo

SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells. (AU)

• Processo FAPESP: 10/06067-1 - Avaliação do silenciamento dos genes SHOC2 e XPO7, associados à resistência à quimioterapia, em linhagens celulares de leucemia linfóide aguda.
• Beneficiário: Vanessa da Silva Silveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado